Tissue-specific knockouts lacking HCN2 in NaV1.8-expressing nociceptors showed normal acute pain thresholds but reduced inflammatory pain and considerably attenuated mechanical, heat, or cold pain following peripheral nerve injury (Emery et al., 2011; Schnorr et al., 2014), attenuated mechanical allodynia in a model of diabetic neuropathy (Tsantoulas et al., 2017), and ameliorated mechanical hypersensitivity in models of migraine (Tsantoulas et al., 2022). This evidence concerns the gene HCN2 and migraine disorder.